The major objective of the proposed research is to identify parameters of cellular alterations associated specifically with the physiological rates of aging. The experimental approach involves manipulation of life span by varying the rates of metabolic expenditure. Life span of the housefly is inversely related to the metabolic rate. The average and maximum life span will be extended by altering the flying activity and the environmental temperature. Cellular changes as reflected by the following parameters will be studied in houseflies undergoing varied rates of aging: (1) lipofuscin accumulation in different postmitotic cell types by fluorescence microscopy, (2) levels of fluorescent substances extracted from flies of different age groups by fluorometry, (3) activities of the lysosomal enzymes by biochemical assays, (4) alterations in cellular fine structure by quantitative techniques of electron microscopy. The results of this study should indicate if cellular alterations in the above parameters respond to the experimental variations in the life span. The potential usefulness of such studies lies in the identification of physiologically significant cellular alterations accompanying aging.